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Doxorubicin


ACCESSION NB: DB00997 (APRD00185)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of daunorubicin. [PubChem]

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Antibiotics Antibiotics, Antineoplastic

ABSORPTION: Not Available

INDICATION:
For the treatment of Koposi's sarcome connected to AIDS.

PHARMACODYNAMICS:
Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

MECHANISM OF ACTION:
Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

PROTEIN BINDING:
70%

TOXICITY:
LD50=21800 ug/kg (rat, subcutaneous)

AFECTED ORGANISMS:
Humans and other mammals